4,4'-[(6-chloro-1,3,5-triazine-2,4-diyl)diimino]bis[5-hydroxy-6-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2,7-disulphonic] acid, sodium salt

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 to 23. October 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-[(6-chloro-1,3,5-triazine-2,4-diyl)diimino]bis[5-hydroxy-6-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2,7-disulphonic] acid, sodium salt

EC Number:

303-152-9

EC Name:

4,4'-[(6-chloro-1,3,5-triazine-2,4-diyl)diimino]bis[5-hydroxy-6-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2,7-disulphonic] acid, sodium salt

Cas Number:

94158-79-9

Molecular formula:

C39H32ClN9O26S8.xNa C39H26ClN9Na6O26S8 as hexasodium salt

IUPAC Name:

sodium 5-[(4-chloro-6-{[8-hydroxy-3,6-disulfonato-7-(2-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}diazen-1-yl)naphthalen-1-yl]amino}-1,3,5-triazin-2-yl)amino]-4-hydroxy-3-(2-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}diazen-1-yl)naphthalene-2,7-disulfonate

Test material form:

solid: particulate/powder

Details on test material:

Reactive Red 230

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 7950 Biberach
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 3.1 - 3.5 kg
- Housing: single
- Diet: Altromin 2123 maintenance diet ad libitum and approx. 15 g hay/day
- Water: deionized chlorinated water ad libitum
- Acclimation period: NA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 21
- Humidity (%): 35 - 75
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 Oct. To: 23 Oct. 1992

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm physiological saline solution
- Time after start of exposure: 24 hours

SCORING SYSTEM:
1, 24, 48, and 72 hours, then at 1 week post treatment

About 24 hours before the start of the study the eyes of all animals to be treated were examined under UV light for possible corneal lesions after instillation of one drop of a 0.01 % fluorescine-sodium solution. Only animals without ocular abnormalities were used for the study.
Every 100 mg Reaktiv-Rot F-66 813 FW was administered once into the conjunctival sac of the left eye of three rabbits. In each case, the untreated eye served as a control. 24 hours after the administration of the test substance and also at the designated examination times at which the treated eyes still showed discharge, or a corneal examination with fluorescine-sodium solution was performed the treated eyes were washed thoroughly with isotonic saline (approx. 37 °C).

The eyes were examined 1, 24, 48 and 72 hours after administration of the test substance. After 24 and 72 hours the cornea was additionally examined under UV-light for corneal lesions after instillation of one drop of a fluorescine-sodium solution (0.01 %). Lesions in cornea, iris and conjunctivae were graded numerically. All other changes were recorded.


1. Conjunctivae

Redness: lids and/or nictitating membranes
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis: lids and/or nictitating membranes
No swelling 0
Any amount different from normal (includes nictating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4


2. Iris
Normal 0
Markedly deepened rugae, congestion, swelling, slight
circumcorneal hyperaemia: or injection: iris still reacting to light
(a sluggish reaction is positive) 1
Haemorrhage, gross destruction, or no reaction to light. 2


3. Cornea

Opacity-degree of density (area most dense taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight
dulling of normal lustre): details of iris clearly visible 1
Easily discernible translucent area: details of iris slightly obscured 2
Nacrous area: no details of iris visible: size of pupil barely discernible 3
Opaque cornea: iris not discernible through the opacity 4

Affected area (opacity or stained by fluorescine test)
No translucense 0
Punctiform to one quarter 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4


TOOL USED TO ASSESS SCORE: fluorescein staining and UV-light 24 and 72 hours after treatment

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritant / corrosive response data:

From one hour up to 24 hours after administration the conjunctiva of the animals showed slight to obvious swelling with partial eversion of lids. Additionally, up to 48 hours after administration evident hyperaemie to diffuse deeper crimson coloured reddenings were noted.

From one hour up to 72 hours after administration the nictating membrane of the animals and the iris of one animal were discoloured red. 72 hours after administration the irritations were reversible.
Additional a clear from the substance discoloured discharge was observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the present study, Reaktiv-Rot F-67787 is not irritating to the eye. According to the classification criteria of Directive 83/467/EEC and the Ordinance on Hazardous Substances the test substance is not subject to labeling requirements.

Executive summary:

Testing for primary irritation in the rabbit eye provides information on ocular lesions after a single administration of the test substance to the conjunctival sac of the eye and serves as a basis for classification and labelling.

 

The present study was conducted according to EC-Guideline B.5. Acute Toxicity Eye Irritation of Directive 84/449/EEC: Commission Directive of April 25,1984 adapting for the sixth time Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of hazardous substances to the technical progressand meets the requirements of OECD Guideline for Testing of Chemicals, 405 "Acute Eye Irritation / Corrosion", OECD 1981.Updated Guideline, adopted : 24th February 1987. Study conducted in compliance with GLP.

 

Based on the results of the present rabbit primary eye irritation studyReaktiv-Rot F-67787 is not irritating to the eye and not subject to labelling requirements.